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Proceedings of the National Academy of Sciences, Vol 92, 9363-9367, Copyright © 1995 by National Academy of Sciences
GP Dimri, X Lee, G Basile, M Acosta, G Scott, C Roskelley, EE Medrano, M Linskens, I Rubelj, O Pereira-Smith, M Peacocke and J Campisi
Normal somatic cells invariably enter a state of irreversibly arrested
growth and altered function after a finite number of divisions. This
process, termed replicative senescence, is thought to be a
tumor-suppressive mechanism and an underlying cause of aging. There is
ample evidence that escape from senescence, or immortality, is important
for malignant transformation. By contrast, the role of replicative
senescence in organismic aging is controversial. Studies on cells cultured
from donors of different ages, genetic backgrounds, or species suggest that
senescence occurs in vivo and that organismic lifespan and cell replicative
lifespan are under common genetic control. However, senescent cells cannot
be distinguished from quiescent or terminally differentiated cells in
tissues. Thus, evidence that senescent cells exist and accumulate with age
in vivo is lacking. We show that several human cells express a
ß-galactosidase, histochemically detectable at pH 6, upon senescence
in culture. This marker was expressed by senescent, but not presenescent,
fibroblasts and keratinocytes but was absent from quiescent fibroblasts and
terminally differentiated keratinocytes. It was also absent from immortal
cells but was induced by genetic manipulations that reversed immortality.
In skin samples from human donors of different age, there was an
age-dependent increase in this marker in dermal fibroblasts and epidermal
keratinocytes. This marker provides in situ evidence that senescent cells
may exist and accumulate with age in vivo.
ARTICLE
A Biomarker that Identifies Senescent Human Cells in Culture and in Aging Skin in vivo
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